The etiology and pathogenesis of malignant hepatomas will be studied with the help of cell and tissue specific markers. These markers are complexes of chromosomal nonhistone proteins with the DNA of the same species (homologous DNA). The complexes were shown to be immunologically cell and tissue specific. We propose to determine the biological and biochemical identities and functions of these markers. More specifically, we will characterize the protein and DNA components of these complexes and we will study their changes during the process of experimental hepatocarcinogenesis. Albino rats will be fed specific diets containing various carcinogens and the qualitative modifications of the chromatin and its components will be determined. Immediate effects of selected carcinogens (transformation) will be investigated in short-term experiments on tissue cultured hepatocytes derived from the livers of young and adult rats. Using such cultures in context with the antigenic nonhistone protein-DNA markers, we will endeavor to develop a sensitive in vitro assay for carcinogenic chemicals.